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Volume 25, Number 10—October 2019
Dispatch

Susceptibility of Influenza A, B, C, and D Viruses to Baloxavir1

Vasiliy P. Mishin, Mira C. Patel, Anton Chesnokov, Juan De La Cruz, Ha T. Nguyen, Lori Lollis, Erin Hodges, Yunho Jang, John Barnes, Timothy Uyeki, Charles T. Davis, David E. Wentworth, and Larisa V. GubarevaComments to Author 
Author affiliations: Centers for Disease Control and Prevention, Atlanta, Georgia, USA (V.P. Mishin, M.C. Patel, A. Chesnokov, J. De La Cruz, H.T. Nguyen, L. Lollis, E. Hodges, Y. Jang, J. Barnes, T. Uyeki, C.T. Davis, D.E. Wentworth, L.V. Gubareva); Battelle Memorial Institute, Atlanta (M.C. Patel, J. De La Cruz, H.T. Nguyen, L. Lollis)

Main Article

Table 1

Drug susceptibility of influenza A, B, C, and D viruses by viral yield reduction assay in MDCK cells*

Type Virus Virus titer, log10 TCID50/mL†
 EC90, nmol/L
Baloxavir, mean ± SD
 Favipiravir
24 hpi 48 hpi 24 hpi 48 hpi 48 hpi
A
 A/Texas/138/2018 (H1N1)pdm09 6.4 ± 0.5 9.1 ± 0.1 0.8 ± 0.2 1.2 ± 0.1 NT
A/Illinois/08/2018 (H1N1)pdm09
 5.8 ± 0.5
 8.9 ± 0.3
2.7 ± 0.5
 3.3 ± 0.2
3,005
B
 B/Maryland/29/2018 3.5 ± 0.5 7.1 ± 0.6 8.9 ± 1.6 5.8 ± 1.1 1,789
B/Iowa/18/2018
 3.5 ± 0.5
 7.6 ± 0.4
13.8 ± 2.0
 7.8 ± 1.7
1,635
C
 C/Taylor/1233/47 <1.5 5.9 ± 0.5 NA 13.0 ± 3.3 27,476
C/Aomori/74
 <1.5
 4.9 ± 0.4
NA
 18.4 ± 6.5
31,603
D D/swine/Oklahoma/13334/2011 4.4 ± 0.3 7.7 ± 0.1 110.2 ± 27.6 98.3 ± 23.9 2,764
D/bovine/Oklahoma/660/2013 4.8 ± 0.0 8.0 ± 0.5 105.6 ± 37.0 64.3 ± 16.2 3,106

*Cell monolayers were inoculated at a multiplicity of infection of 0.0005 and virus was allowed to adsorb for 1 h. Virus inoculum was removed, serially diluted drug (baloxavir: 0.5–500 nmol/L; favipiravir: 310–318,000 nmol/L) was added, and cells were incubated at 33°C in a 5% CO2 incubator. At 24 and 48 hpi, cell culture supernatants were harvested to determine infectious virus titers. Replication of influenza A and B viruses was detected by neuraminidase activity (Fluor-NA Kit; Applied Biosystems, https://www.thermofisher.com), and replication of influenza C and D viruses by esterase activity (3-acetyl-umbelliferone in 20 mmol/L Tris-HCl, pH 8.0, reaction buffer (Sigma-Aldrich, https://www.sigmaaldrich.com). The EC90 corresponds to a drug concentration causing a 90% reduction in virus titer compared with control wells without drug. The EC90 for each virus and drug were determined by using nonlinear regression analysis (GraphPad, https://www.graphpad.com). For baloxavir, results are shown as mean ± SD of 3 independent experiments; favipiravir results are shown as single or average of 2 independent experiments. EC90, 90% effective concentration; hpi, hours postinfection; NA, not applicable; NT, not tested; TCID50, 50% tissue culture infectious dose.
†Virus titers were determined in control wells without drug.

Main Article

1Preliminary results from this study were presented at the 6th International Society for Influenza and Other Respiratory Virus Diseases Antiviral Group Conference; November 13–15, 2018; Rockville, Maryland, USA.

Page created: September 17, 2019
Page updated: September 17, 2019
Page reviewed: September 17, 2019
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